Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects

{ 'DOI': '10.1038/s41401-022-00895-6', 'ISSN': ['1671-4083', '1745-7254'], 'URL': 'http://dx.doi.org/10.1038/s41401-022-00895-6', 'abstract': '<jats:title>Abstract</jats:title><jats:p>VV116 (JT001) is an oral drug candidate of ' 'nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to ' 'evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral ' 'doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and ' 'safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose ' 'study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, ' 'FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo ' 'were administered per protocol requirements. Blood samples were collected at the scheduled ' 'time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in ' 'plasma and calculated for the PK parameters. In SAD, AUC and ' '<jats:italic>C</jats:italic><jats:sub>max</jats:sub> increased in an approximately ' 'dose-proportional manner in the dose range of 25–800\u2009mg. ' '<jats:italic>T</jats:italic><jats:sub>1/2</jats:sub> was within 4.80–6.95\u2009h. In MAD, the ' 'accumulation ratio for <jats:italic>C</jats:italic><jats:sub>max</jats:sub> and AUC indicated ' 'a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect ' 'on <jats:italic>C</jats:italic><jats:sub>max</jats:sub> and AUC of VV116. No serious adverse ' 'event occurred in the studies, and no subject withdrew from the studies due to adverse ' 'events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which ' 'supports the continued investigation of VV116 in patients with COVID-19.</jats:p>', 'alternative-id': ['895'], 'assertion': [ { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'Received', 'name': 'received', 'order': 1, 'value': '18 February 2022'}, { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'Accepted', 'name': 'accepted', 'order': 2, 'value': '3 March 2022'}, { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'First Online', 'name': 'first_online', 'order': 3, 'value': '16 March 2022'}, { 'group': {'label': 'Competing interests', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 1, 'value': 'HQD and GHT are the employees of Vigonvita Life Science Co., Ltd, the sponsor ' 'of the study. JM, ZBZ, and NL are the employees of Shanghai Junshi Biosciences ' 'Co., Ltd., the parent company of the co-sponsor Shanghai JunTop Biosciences ' 'Co., Ltd. YCX, JSS, and HLJ filed a patent application on antiviral nucleoside ' 'analogs. The remaining authors declare no competing interests.'}], 'author': [ {'affiliation': [], 'family': 'Qian', 'given': 'Hong-jie', 'sequence': 'first'}, {'affiliation': [], 'family': 'Wang', 'given': 'Yu', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Zhang', 'given': 'Meng-qi', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Xie', 'given': 'Yuan-chao', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Wu', 'given': 'Qing-qing', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Liang', 'given': 'Li-yu', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Cao', 'given': 'Ye', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Duan', 'given': 'Hua-qing', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Tian', 'given': 'Guang-hui', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Ma', 'given': 'Juan', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Zhang', 'given': 'Zhuo-bing', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Li', 'given': 'Ning', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Jia', 'given': 'Jing-ying', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Zhang', 'given': 'Jing', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Aisa', 'given': 'Haji Akber', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Shen', 'given': 'Jing-shan', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Yu', 'given': 'Chen', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Jiang', 'given': 'Hua-liang', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Zhang', 'given': 'Wen-hong', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Wang', 'given': 'Zhen', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Liu', 'given': 'Gang-yi', 'sequence': 'additional'}], 'container-title': 'Acta Pharmacologica Sinica', 'container-title-short': 'Acta Pharmacol Sin', 'content-domain': {'crossmark-restriction': False, 'domain': ['link.springer.com']}, 'created': {'date-parts': [[2022, 3, 16]], 'date-time': '2022-03-16T10:05:53Z', 'timestamp': 1647425153000}, 'deposited': { 'date-parts': [[2022, 11, 30]], 'date-time': '2022-11-30T10:09:03Z', 'timestamp': 1669802943000}, 'indexed': {'date-parts': [[2024, 1, 2]], 'date-time': '2024-01-02T20:43:09Z', 'timestamp': 1704228189820}, 'is-referenced-by-count': 33, 'issue': '12', 'issued': {'date-parts': [[2022, 3, 16]]}, 'journal-issue': {'issue': '12', 'published-print': {'date-parts': [[2022, 12]]}}, 'language': 'en', 'license': [ { 'URL': 'https://creativecommons.org/licenses/by/4.0', 'content-version': 'tdm', 'delay-in-days': 0, 'start': { 'date-parts': [[2022, 3, 16]], 'date-time': '2022-03-16T00:00:00Z', 'timestamp': 1647388800000}}, { 'URL': 'https://creativecommons.org/licenses/by/4.0', 'content-version': 'vor', 'delay-in-days': 0, 'start': { 'date-parts': [[2022, 3, 16]], 'date-time': '2022-03-16T00:00:00Z', 'timestamp': 1647388800000}}], 'link': [ { 'URL': 'https://www.nature.com/articles/s41401-022-00895-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41401-022-00895-6', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41401-022-00895-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '297', 'original-title': [], 'page': '3130-3138', 'prefix': '10.1038', 'published': {'date-parts': [[2022, 3, 16]]}, 'published-online': {'date-parts': [[2022, 3, 16]]}, 'published-print': {'date-parts': [[2022, 12]]}, 'publisher': 'Springer Science and Business Media LLC', 'reference': [ { 'DOI': '10.1093/cid/ciaa1041', 'author': 'SA Olender', 'doi-asserted-by': 'publisher', 'first-page': 'e4166', 'journal-title': 'Clin Infect Dis', 'key': '895_CR1', 'unstructured': 'Olender SA, Perez KK, Go AS, Balani B, Price-Haywood EG, Shah NS, et al. 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